Vitamin D Deficiency Is Associated With Poor Ovarian Stimulation Outcome in PCOS but Not Unexplained Infertility

J Clin Endocrinol Metab. 2019 Feb 1;104(2):369-378. doi: 10.1210/jc.2018-00750.


Context: The impact of vitamin D deficiency on the success of ovarian stimulation according to underlying infertility diagnosis has not been investigated.

Objective: To evaluate the relationship between vitamin D deficiency and reproductive outcomes after ovarian stimulation in women with either polycystic ovary syndrome (PCOS) or unexplained infertility.

Design: Retrospective cohort study.

Setting: Analysis of randomized controlled trial (RCT) data.

Participants: Participants from the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) RCT (n = 607); participants from the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) RCT of unexplained infertility (n = 647).

Interventions: Serum 25(OH)D levels measured in banked sera.

Main outcome measures: Primary: live birth; secondary: ovulation (PPCOS II), pregnancy, and early pregnancy loss.

Results: In PPCOS II, subjects with vitamin D deficiency [25(OH)D < 20 ng/mL or 50 nmol/L] were less likely to ovulate (adjusted OR, 0.82; 95% CI, 0.68 to 0.99; P = 0.04) and experienced a 40% lower chance of live birth (adjusted OR, 0.63; 95% CI, 0.41 to 0.98; P = 0.04) than those not deficient. In AMIGOS, no significant association between vitamin D deficiency and live birth was noted. In pregnant subjects from both studies, vitamin D deficiency was associated with elevated risk of early pregnancy loss (OR, 1.6; 95% CI, 1.0 to 2.6; P = 0.05).

Conclusions: In this investigation of women pursuing ovarian stimulation, the association between vitamin D deficiency and diminished live birth relied on carrying the diagnosis of PCOS and was not observed in unexplained infertility. Given the generally modest success of ovarian stimulation, addressing vitamin D deficiency may prove an important treatment adjunct for many infertile women.

Trial registration: NCT00719186 NCT01044862.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Humans
  • Infertility, Female / blood
  • Infertility, Female / etiology
  • Infertility, Female / therapy*
  • Ovulation Induction / statistics & numerical data*
  • Polycystic Ovary Syndrome / blood
  • Polycystic Ovary Syndrome / complications*
  • Pregnancy
  • Pregnancy Outcome*
  • Randomized Controlled Trials as Topic
  • Retrospective Studies
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / etiology*
  • Young Adult


  • Vitamin D

Associated data